猴痘——對大流行病整備和性健康系統能力之發人深省的哨兵
資料來源：Matthew R. Golden & Judith N. Wasserheit / n engl j med 387;20 / 2022年11月17 日 / 財團法人台灣紅絲帶基金會編譯
2022 年 5 月至 10 月中旬，臨床醫生在 102 個通常不受病毒影響的國家/地區診斷出超過 72,000 例猴痘病例（見地圖）。 這種新的流行病給已經飽受Covid-19打擊的公共衛生和醫療保健系統帶來了壓力。 它還強調了從 HIV 和 Covid-19 中吸取的——有時被忽視的——教訓，並說明了美國性健康基礎設施和大流行防範工作的不足。
在當前的大流行中，我們堅信猴痘應被視為一種性傳播感染 (STI)。可以從精液、直腸和口腔液體中分離出病毒，並且大多數患者出現了常伴有的肛門生殖器或口咽部病變與 HIV 或其他性傳播感染症(STIs)。是否將猴痘歸類為 STI 一直是一個有爭議的問題。儘管最近在撒哈拉以南非洲發生的猴痘流行病的特點是一些患者出現生殖器潰瘍，受影響人群從兒童轉向年輕人，但很少有人關注性傳播，儘管非洲研究人員呼籲探討這一問題。該病毒也可以透過與病變的非性接觸傳播，可能透過接觸沒有病變的感染者的粘膜傳播，並且不太常見，透過污染物和呼吸道分泌物傳播。
將感染歸類為 STI 或非 STI 的普遍傾向過於簡單化。許多常見的 STI 可以透過非性接觸傳播，患有某些 STI（例如梅毒）的人通常會出現非生殖器病變。人類乳突病毒、HIV、皰疹、梅毒和潛在的淋病可透過陰道性交、肛交和口交以外的接觸方式傳播。相反，許多通常不屬於 STI 的感染可以透過性傳播（例如志賀氏菌、玆卡病毒和伊波拉病毒）。 如果沒有性傳播，目前的猴痘大流行可能不會發生——例如，不像最近的伊波拉或玆卡病毒的地方流行——人們可以透過改變他們的性行為來大大降低他們感染猴痘的風險。因此，我們認為將猴痘視為性傳播感染是恰當的，同時承認並非所有病例都是性傳播的，而且並非所有猴痘流行都主要由性行為驅動。
與猴痘相關的公共衛生傳播也同樣存在爭議。目前的流行病主要集中在男男性行為者 (MSM) 中，包括那些感染 HIV 或正在使用 HIV 暴露前預防措施的人。在可獲得數據的美國病例中，98% 是出生時被指定為男性的人，93% 是男同性戀或雙性戀男性。點亮猴痘在這個人群中的濃度是污名化的。鑑於對 MSM 的廣泛歧視，這種恐懼是有根據的。然而，HIV 和 Covid-19 全球流行都證明了向公眾提供清晰準確信息的必要性，這使處於更高風險中的人們和社區能夠保護自己。此外，承諾與受影響社區合作提供完整、準確的信息對於維持公眾的信任至關重要。對抗 HIV 的鬥爭是由要求真相和透明度的 MSM 社區的領導人塑造的。我們認為猴痘大流行同樣需要清晰的溝通。科學家也應該謙虛並傳達其不確定性。我們不知道這種流行病將如何演變。猴痘可能會傳播到其他人群，包括來自邊緣化群體的女性，或者成為地方病。公眾需要了解這些可能性及其影響。
2022 年大流行期間各國的猴痘病例分佈。來自疾病控制和預防中心。數據截至 2022 年 10 月 17 日。圓圈的大小反映了每個國家/地區的相對病例數。
Covid-19 的教訓為猴痘反應提供了信息。 在猴痘大流行早期，由於檢測和疫苗供應不足、繁瑣的檢測審批程序以及獲得治療的繁瑣文書工作要求，醫療服務受到限制。解決這些問題的進展非常迅速。商業實驗室擴大了猴痘 PCR 檢測，聯邦機構降低了使用 tecovirimat 的障礙。在 Covid-19 之後，許多地區加強了公共衛生系統的組成部分。監控系統更好；衛生部門內部以及衛生部門、疾病控制與預防中心、衛生保健組織和公眾之間的溝通得到改善；許多衛生保健組織為突發公共衛生事件做好了更充分的準備；用於管理和使用疫苗的基礎設施更加強大。儘管美國的猴痘疫苗供應最初不足，但皮內免疫接種的規模擴大（所需疫苗數量少於皮下注射）已經擴大了有效供應。
但其他部份仍沒有學會。流行病的頻率、嚴重程度和規模都在增加，但機構中的公共和私營部門仍然沒有做好充分的準備。研究顯示，隨著時間的推移，流行病的影響通常會集中在弱勢和邊緣化人群中，從而擴大不平等。美國的猴痘病例越來越多地集中在黑人和拉丁裔人群中，但美國尚未充分投資於開發和實施創新策略以儘早接觸到這些群體——從經濟、政治、道德和疾病控制的角度來看，這是明智的做法。此外，很明顯，最好的生物醫學工具，如疫苗和抗病毒藥物，必須與幫助人們降低風險和有效使用這些工具的政策和計畫一起實施。然而，政策制定者和社區往往在採取這些介入措施方面行動遲緩。研究和經驗還顯示，保護美國人需要支持低收入和中等收入國家的大流行病預防和控制，而大多數大流行病原體都是在這些國家出現的。但美國在加強監測系統和為這些國家提供猴痘（和 Covid-19）檢測、治療和疫苗的公平獲取方面幾乎沒有作為。儘管高品質的數據對於形成臨床和公共衛生決策是必要的，但美國在將研究工作與大流行病的準備和應對相結合方面做得還不夠——這一結論得到了 JYNNEOS 疫苗和 tecovirimat 缺乏明確療效數據的支持，而這些卻是針對猴痘的主要生物醫學介入措施。
最後，美國的猴痘應對工作因公共衛生基礎設施不足而受到阻礙。公共衛生機構沒有可在緊急情況下迅速部署用於病例調查、接觸者追踪、疾病監測、社區疫苗接種活動和相關活動的資金來源。應急響應需要一支資源充足、穩定、訓練有素、可以迅速啟動的公共衛生隊伍。
新的大流行病還凸顯了該國性健康基礎設施的不足。在 Covid-19 大流行之前，美國最常見的三種報告疾病是性傳播感染。 2018 年 STI 導致近 160 億美元的直接醫療費用。在金縣，我們的性健康診所——該州唯一的一家——是華盛頓州最大的猴痘診斷和治療臨床站點。我們迅速擴大了疫苗接種活動，每天為大約 350 名患者接種疫苗，其中幾乎所有患者都是 MSM 或跨性別者。全國許多性健康診所都採取了類似的舉措。但許多城市幾乎沒有專門的性健康服務。這種差距的影響超出了猴痘。它削弱了我們解決美國迅速增加的先天性梅毒發生率的能力，並阻止我們充分利用科學進步來控制愛滋病毒。
性健康診所是必不可少的，但有效的 STI 控制需要整合公共衛生系統和方法、更廣泛的醫療保健系統以及受影響社區的努力。儘管婦女和兒童首當其衝地承受性傳播感染的長期後果，但愛滋病毒、梅毒、淋病和猴痘等感染對男男性接觸者和跨性別者的影響尤為嚴重。解決這種差異需要系統地詢問所有患者的性別認同、性取向和性行為；將此信息記錄在可在安全電子健康記錄中查詢的字段中；並使用由此產生的數據提供高品質的 STI照護，包括向需要的人提供疫苗、檢測、治療和暴露前預防。它還需要與社區合作以接觸黑人和拉丁裔 MSM，並建立夥伴關係以開展外展活動和臨床基礎設施，以滿足受影響最嚴重人群的需求。美國和許多其他國家的新猴痘病例數量正在減少。 但現在宣布勝利還為時過早。公共和私營部門的領導人也必須從這一新的流行病中吸取教訓。在 Covid-19 和 40 多年的 HIV 控制努力之後，猴痘大流行是另一個哨兵事件，它突出地顯示迫切需要建立和維持公共衛生和臨床基礎設施，以加強大流行的預防和應對，並使我們能夠有效地面對增加的 STI 流行。
作者提供的披露表可在 NEJM.org 獲取。
來自愛滋病和性病中心 (M.R.G.)、大流行防範聯盟 (J.N.W.)、醫學系過敏和傳染病科 (M.R.G., J.N.W.) 和全球衛生系 (J.N.W.)，華盛頓大學公共衛生部門——西雅圖和金縣 (M.R.G.)，以及弗雷德哈欽森癌症中心 (J.N.W.)——都在西雅圖。
本文於 2022 年 11 月 2 日發表在 NEJM.org。
Monkeypox — A Sobering Sentinel for Pandemic Preparedness and Sexual Health System Capacity
Matthew R. Golden, M.D., M.P.H., and Judith N. Wasserheit, M.D., M.P.H. / n engl j med 387;20 nejm.org November 17, 2022
Between May and mid-October 2022, clinicians diagnosed more than 72,000 cases of monkeypox in 102 countries that aren’t typically affected by the virus (see map). This new pandemic has strained public health and health care systems already battered by Covid-19. It has also highlighted lessons learned — and sometimes ignored — from HIV and Covid-19 and has illustrated the inadequacy of sexual health infrastructure and pandemic preparedness in the United States.
In the current pandemic, we strongly believe monkeypox should be considered a sexually transmitted infection (STI).2 The virus can be isolated from semen and rectal and oral fluids, and most patients have presented with anogenital or oropharyngeal lesions, frequently in association with HIV or other STIs. Whether to categorize monkeypox as an STI has been a controversial question. Although recent monkeypox epidemics in sub-Saharan Africa have been characterized by genital ulcers in some patients and a shift in the affected population from children to young adults, little attention has been focused on sexual transmission, despite calls from African investigators to explore this issue. The virus is also transmissible through nonsexual contact with lesions, possibly through contact with the mucosa of infected persons without lesions, and, much less commonly, through fomites and perhaps respiratory secretions.
The common tendency to categorize infections as either STIs or not STIs is overly simplistic. Many common STIs can be transmitted through nonsexual contact, and people with some STIs, such as syphilis, commonly present with nongenital lesions. Human papillomavirus, HIV, herpes, syphilis, and potentially gonorrhea are transmissible through modes of contact other than vaginal, anal, and oral sex. Conversely, many infections that aren’t typically classified as STIs can be transmitted through sex (e.g., shigella, Zika, and Ebola). The current monkeypox pandemic probably wouldn’t have occurred in the absence of sexual transmission — unlike the recent Ebola or Zika epidemics, for example — and people can substantially reduce their risk of monkeypox by changing their sexual behavior. We therefore believe it’s appropriate to consider monkeypox an STI while acknowledging that not every case is sexually transmitted and not every monkeypox epidemic is driven primarily by sex.
Monkeypox-related public health communications have proven similarly controversial. The current pandemic is concentrated among men who have sex with men (MSM), including those who have HIV or are using preexposure prophylaxis for HIV. Among U.S. cases for which data are available, 98% have been in people assigned male sex at birth, and 93% have been in gay or bisexual men.5 Some public health officials and community representatives have expressed concern that communications highlighting the concentration of monkeypox in this population are stigmatizing. This fear is well founded, given widespread discrimination against MSM. Both the HIV and Covid-19 pandemics, however, have demonstrated the necessity of providing the public with clear and accurate information, which equips people and communities at increased risk to protect themselves. Moreover, the commitment to providing complete, accurate information in partnership with affected communities is essential to maintaining the public’s trust. The fight against HIV was shaped by leaders in the MSM community who demanded truth and transparency. We believe the monkeypox pandemic similarly demands clear communication. Scientists should also be humble and communicate uncertainty. We don’t know how this pandemic will evolve. Monkeypox could expand to other populations, including women from marginalized groups, or become endemic. The public needs to know about these possibilities and their implications.
Distribution of Monkeypox Cases by Country in the 2022 Pandemic. From the Centers for Disease Control and Prevention.1 Data are as of October 17, 2022. The size of the circles reflects the relative number of cases in each country.
Lessons from Covid-19 have informed the monkeypox response. Early in the monkeypox pandemic, access to care was limited by inadequate supplies of tests and vaccines, burdensome approval processes for testing, and onerous paperwork requirements to obtain treatment. Progress in addressing these problems has been rapid. Commercial laboratories scaled up monkeypox PCR testing, and federal agencies reduced the barriers to tecovirimat access. Many regions have strengthened components of their public health systems in the wake of Covid-19. Surveillance systems are better; communication within health departments and among health departments, the Centers for Disease Control and Prevention, health care organizations, and the public has improved; many health care organizations are better prepared for public health emergencies; and infrastructure for managing and administering vaccines is stronger. Although the U.S. monkeypox vaccine supply was initially inadequate, scale-up of intradermal immunizations, which require smaller quantities of vaccine than subcutaneous injections, has expanded the effective supply.
Other lessons haven’t been learned. Pandemics have increased in frequency, severity, and scale, yet public- and private-sector institutions remain inadequately prepared for them. Research shows that the effects of pandemics typically concentrate over time in vulnerable and marginalized populations, thereby amplifying inequities. U.S. monkeypox cases have increasingly been concentrated among Black and Latinx people, yet the United States hasn’t adequately invested in developing and implementing innovative strategies for reaching these groups early — the wise approach from economic, political, moral, and disease-control perspectives. Moreover, it’s clear that the best biomedical tools, such as vaccines and antivirals, must be implemented alongside policies and programs that help people reduce their risk and use these tools effectively. Yet policymakers and communities are often slow to adopt these interventions. Research and experience also show that protecting Americans requires supporting pandemic prevention and control in low- and middle-income countries, where most pandemic pathogens emerge. But the United States has done little to strengthen surveillance systems and provide equitable access to monkeypox (and Covid-19) testing, treatment, and vaccines in such countries. Although high quality data are necessary to inform clinical and public health decision making, the United States hasn’t done enough to integrate research efforts with pandemic preparedness and response — a conclusion supported by the lack of definitive efficacy data for both the JYNNEOS vaccine and tecovirimat, the primary biomedical interventions for monkeypox.
Finally, the U.S. monkeypox response has been hampered by inadequate public health infrastructure. Public health agencies don’t have sources of funding that can be deployed rapidly in an emergency for case investigation, contact tracing, disease surveillance, community vaccination events, and related activities. Emergency response requires an adequately resourced, stable, welltrained public health workforce that can be activated rapidly.
The new pandemic has also highlighted the inadequacy of the country’s sexual health infrastructure. Before the Covid-19 pandemic, the three most common reportable diseases in the United States were STIs. STIs resulted in nearly $16 billion in direct medical costs in 2018. In King County, our sexual health clinic — the only one in the state — is the largest clinical site for diagnosing and treating monkeypox in Washington State. We rapidly scaled up vaccination activities to immunize approximately 350 patients per day, nearly all of them MSM or transgender people. Many sexual health clinics throughout the country have taken similar initiatives. But many cities have virtually no specialty sexual health services. This gap has implications that extend beyond monkeypox. It undermines our ability to address rapidly increasing rates of congenital syphilis in the United States and prevents us from fully capitalizing on scientific advances to control HIV.
Sexual health clinics are essential, but effective STI control requires integrating public health systems and approaches, the wider health care system, and the efforts of affected communities. Although women and children bear the brunt of long-term consequences from STIs, infections such as HIV, syphilis, gonorrhea, and monkeypox disproportionately affect MSM and transgender people. Addressing this disparity requires systematically asking all patients about their gender identity, sexual orientation, and sexual behavior; recording this information in fields that can be queried in secure electronic health records; and using the resulting data to provide high-quality STI care, including delivery of vaccines, testing, treatment, and preexposure prophylaxis to people who need them. It also requires engaging with communities to reach Black and Latinx MSM and forming partnerships to develop outreach activities and clinical infrastructure that meet the needs of the most affected populations. The number of new monkeypox cases in the United States and many other countries is now decreasing. But it’s too early to declare victory. Public- and private-sector leaders must also learn from this new pandemic. Coming on the heels of Covid-19 and more than 40 years of HIV control efforts, the monkeypox pandemic is another sentinel event that highlights the urgent need to build and sustain public health and clinical infrastructure that strengthens pandemic prevention and response and enables us to confront the growing STI epidemics effectively.
Disclosure forms provided by the authors are available at NEJM.org.
From the Center for AIDS and STD (M.R.G.), the Alliance for Pandemic Preparedness (J.N.W.), the Division of Allergy and Infectious Diseases, Department of Medicine (M.R.G., J.N.W.), and the Department of Global Health (J.N.W.), University of Washington, Public Health — Seattle and King County (M.R.G.), and the Fred Hutchinson Cancer Center (J.N.W.) — all in Seattle.
This article was published on November 2, 2022, at NEJM.org.